Cardiovascular disease remains a leading cause of death throughout the world, with many dying outside the hospital due to cardiac arrest. Although oxidants may play an important role in this major cardiovascular disease, little has been done to examine what role traditional vs. nontraditional antioxidants may play in its acute treatment. During the past year, our group investigated cardioprotective effects of Scutellaria baicalensis, a Chinese medicinal herb. We reported that an extract of Scutellaria baicalensis dose-dependently attenuated reactive oxygen species in cardiomyocytes and decreased cell death. We were particularly excited to observe that Scutellaria baicalensis extract rapidly quenched reactive oxygen species generated in mitochondria. The ability to gain rapid access to intracellular sites, such as mitochondria, and attenuate reactive oxygen species is a significant advantage, a characteristic that may be lacking in antioxidants currently in use. In separate studies, we observed that quercetin, a plant flavonoid, inhibited endothelin-1 and stimulated tissue plasminogen activator in vascular endothelial cells. Thus, we hypothesize that flavonoids of Scutellaria baicalensis have significant antioxidant potential, and they regulate the concentration of endothelial vasoactive mediators. Heart disease is a complex multifactorial disorder with a variety of underlying causes and risk factors. In the development of ischemic heart disease, the site of initial injury is the vascular endothelium. During later stages, ischemic and reperfusion injury to cardiomyocytes lead to loss of contractility and cell death. We propose to investigate in vitro pharmacological effects of Scutellaria baicalensis in two experimental models: embryonic chick cardiomyocytes, and human umbilical vein endothelial cells. In the proposed project, we will identify active flavonoids of Scutellaria baicalensis and investigate their 1) antioxidant action in cardiomyocytes, and 2) pharmacological effects on vasoactive mediators in endothelial cells. We will test whether Scutellaria baicalensis extract and its flavonoids (baicalein and wogonin, skullcapflavone I, and skullcapflavone II) act as antioxidants in cardiomyocytes, and test whether Scutellaria baicalensis extract and its flavonoids change the concentration of thrombin-stimulated endothelin-1, and tissue plasminogen activator in vascular endothelial cells. In addition, antioxidant activity comparison will be made between Scutellaria baicalensis and American ginseng. The results of our project will be used to develop potential new therapeutic agents from active components of Scutellaria baicalensis.